1. Field of the Invention
Immune system genes and their cognate receptors, have a functional role in the wiring and function of the nervous system. Specific brain functions for immune related molecules and cognate receptor systems include memory functions and other processes occurring in the brain both in development and adulthood that are referred to as “synaptic plasticity”. Drugs commonly used to treat autoimmune diseases, infection or tissue rejection associated with transplantation will have therapeutic action in the treatment of disorders of the Central Nervous System (CNS). These drugs function to alter the interaction of neurons expressing immune related molecules, Gp49, PIR, PIRA, PIRB, LIR, NKR-P1, NKp46, Digr1, ILT, MIR, KIR, class I MHC and other immune-related receptors.
2. Background
Diversity in the immune system is used to establish an essentially unlimited array of complex receptor-ligand interactions. In B cells, the interactions occur between the variable region of antibodies and different antigens. In T cells, the interactions occur between the variable region of T cell receptors (TCRs) and cell surface proteins encoded by a set of genes termed the major histocompatibility complex (MHC). MHC molecules play an essential role in immunologic diversity by presenting on the cell surface peptides that are derived from intracellular proteolysis; these peptides can then in turn be recognized by TCRs. There are two different types of MHC molecules: class I, which present peptides to cytotoxic T cells (CD8+ cells), and class II, which present peptides to helper T cells (CD4+ cells). MHC I molecules function classically as heterotrimers consisting of a heavy chain, which presents peptide, and an invariant light chain, termed β2-microglobulin. TCRs function as heterodimers that associate with a number of integral membrane signaling proteins and are important in maintaining the integrity of the immune system.
Neuronal cells, including brain cells are non-dividing cells and there is little in the understanding of the complex networks that exist between cells of the nervous system. The mechanisms that cause many neurological disorders are poorly understood. It would be of major benefit if molecules involved in neurological disorders, neural networking and regeneration of nerve cells, could be identified.